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Cancers 2017, 9(8), 109; https://doi.org/10.3390/cancers9080109

Understanding Resistance Mechanisms and Expanding the Therapeutic Utility of PARP Inhibitors

1
Department of Hematology-Oncology, National University Cancer Institute of Singapore, National University Hospital, Singapore 119228, Singapore
2
Cancer Science Institute Singapore, Women’s Cancer Research Group, Singapore 117599, Singapore
*
Author to whom correspondence should be addressed.
Academic Editor: Eddy S. Yang
Received: 16 July 2017 / Revised: 18 August 2017 / Accepted: 18 August 2017 / Published: 22 August 2017
(This article belongs to the Special Issue DNA Repair Pathways in Cancer)
Full-Text   |   PDF [577 KB, uploaded 23 August 2017]   |  

Abstract

Poly-(ADP-ribose) polymerase (PARP) inhibitors act through synthetic lethality in cells with defects in homologous recombination (HR) DNA repair caused by molecular aberrations such as BRCA mutations, and is approved for treatment in ovarian cancer, with promising clinical activity against other HR defective tumors including breast and prostate cancers. Three PARP inhibitors have been FDA approved, while another two have shown promising activity and are in late stage development. Nonetheless, both primary and secondary resistance to PARP inhibition have led to treatment failure, and the development of predictive biomarkers and the ability to identify and overcome mechanisms of resistance is vital for optimization of its clinical utility. Additionally, there has been evidence that PARP inhibition may have a therapeutic role beyond HR deficient tumors which warrants further investigation, both as single agent and in combination with other therapeutic modalities like cytotoxic chemotherapy, radiation, targeted therapy and immunotherapy. With new strategies to overcome resistance and expand its therapeutic utility, PARP inhibitors are likely to become a staple in our armamentarium of drugs in cancer therapeutics. View Full-Text
Keywords: PARP inhibitors; targeted therapy PARP inhibitors; targeted therapy
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Lim, J.S.J.; Tan, D.S.P. Understanding Resistance Mechanisms and Expanding the Therapeutic Utility of PARP Inhibitors. Cancers 2017, 9, 109.

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